PROJECT SUMMARY Adolescence is most strikingly characterized by the pubertal growth spurt. It is also a time when the prevalence of depressive and anxiety disorders increases dramatically, a fact reflected in the widespread use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). In fact, antidepressants comprise the third most commonly prescribed medication class in this age group. In a recent publication, we reported that SSRIs, fluoxetine specifically, were associated with longitudinal growth suppression in older adolescents prospectively followed for two years. This was consistent with a case series showing suppression of growth and growth hormone (GH) neurosecretory function in four SSRI-treated adolescents and with a placebo-controlled clinical trial in children and adolescents showing growth suppression during fluoxetine treatment. In further studies from our lab, we confirmed in risperidone-treated boys, that SSRI use was associated with growth suppression, most pronounced during Tanner stages 3 and 4, which is plausible given that height velocity peaks during these Tanner stages. We further found that change in the serum concentration of insulin growth factor 1 (IGF-1) is most different between adolescents who start SSRIs and those who stop them, again implicating GH dysfunction in SSRI-induced growth suppression. These findings have led us to propose, in this exploratory research grant application, to examine short- (i.e., 8 weeks) and intermediate-term (i.e., 6 months) changes in GH function indicators (i.e., IGF-1 and insulin growth factor binding protein 3 [IGFBP-3]), in Tanner stages 2-4 adolescents starting treatment with SSRIs. We will focus on examining differences between fluoxetine and sertraline, the latter having not been associated with longitudinal growth suppression. We further seek preliminary evidence that these changes mediate SSRI- induced growth suppression. In sum, the proposed study will be the first to investigate the mechanism underlying SSRI-induced longitudinal growth suppression, shedding light on a currently little-recognized side effect of a widely and increasingly used medication class.